The G-protein-coupled receptor (GPCR) family of proteins have important roles in signal transduction and cellular response to extracellular stimuli. For this reason GPCRs are the target of many pharmaceuticals. The μ opioid receptor (MUR) is a GPCR that is the dominant target of opioids, many of which are potent analgesics widely used for the treatment of severe and chronic pain, e.g., morphine. Opioid use has soared in recent years and human MUR has been linked to abuse and many notorious side effects, including addiction and deadly respiratory depression.
The molecular mechanisms governing GPCR function remains obscure despite the profound insights obtained recently from multiple high-resolution crystal structures. Drug development and the study of the molecular mechanisms of GPCRs are impeded by limited solubility and difficulty in isolating sufficient quantities of functional receptors. These difficulties are caused in part by the large numbers of hydrophobic residues on the transmembrane, lipid-contacting protein exterior. Functional studies of MUR, and other GPCRs, could be carried out or greatly accelerated if forms of the protein existed that are water soluble, retain properties of native protein functionality, and are easily obtained in large quantity.